PDBsum entry: 1zi5

Transferase

PDB id: 1zi5

Contents

Protein chain

264 a.a. *

Ligands

DR3

UDP

Metals

_HG ×6

Waters ×213

* Residue conservation analysis

PDB id:

1zi5

Name:

Transferase

Title:

Crystal structure of human n-acetylgalactosaminyltransferase complexed with h type i trisaccharide

Structure:

Histo-blood group abo system transferase (nagat) glycoprotein-fucosylgalactoside alpha-n- acetylgalactosaminyltransferase. Chain: a. Synonym: fucosylglycoprotein alpha-n-acetylgalactosaminyltr (histo-blood group a transferase) (a transferase). Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: abo. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.55Å R-factor: 0.211 R-free: 0.226

Authors:

J.A.Letts,N.L.Rose,Y.R.Fang,C.H.Barry,S.N.Borisova,N.O.Seto, M.M.Palcic,S.V.Evans

Key ref:

J.A.Letts et al. (2006). Differential Recognition of the Type I and II H Antigen Acceptors by the Human ABO(H) Blood Group A and B Glycosyltransferases. J Biol Chem, 281, 3625-3632. PubMed id: 16326711 DOI: 10.1074/jbc.M507620200

Date:

26-Apr-05 Release date: 13-Dec-05

Protein chain

P16442  (BGAT_HUMAN) -  Histo-blood group ABO system transferase

Seq: 354 a.a.

Struc: 264 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.4.1.37 - Fucosylgalactoside 3-alpha-galactosyltransferase.
• Reaction: UDP-galactose + alpha-L-fucosyl-(1->2)-D-galactosyl-R = UDP + alpha-D- galactosyl-(1->3)-(alpha-L-fucosyl-(1->2))-D-galactosyl-R

UDP-galactose + alpha-L-fucosyl-(1->2)-D-galactosyl-R (Bound ligand (Het Group name = DR3) matches with 59.46% similarity) = UDP (Bound ligand (Het Group name = UDP) corresponds exactly) + alpha-D- galactosyl-(1->3)-(alpha-L-fucosyl-(1->2))-D-galactosyl-R

• Enzyme class 2: E.C.2.4.1.40 - Glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase.
• Reaction: UDP-N-acetyl-D-galactosamine + glycoprotein-alpha-L-fucosyl-(1->2)-D- galactose = UDP + glycoprotein-N-acetyl-alpha-D-galactosaminyl-(1->3)- (alpha-L-fucosyl-(1->2))-D-galactose

UDP-N-acetyl-D-galactosamine + glycoprotein-alpha-L-fucosyl-(1->2)-D- galactose = UDP (Bound ligand (Het Group name = UDP) corresponds exactly) + glycoprotein-N-acetyl-alpha-D-galactosaminyl-(1->3)- (alpha-L-fucosyl-(1->2))-D-galactose

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (1 term)
• Biological process: carbohydrate metabolic process (1 term)
• Biochemical function: transferase activity, transferring hexosyl groups (1 term)

reference

DOI no: 10.1074/jbc.M507620200

J Biol Chem 281:3625-3632 (2006)

PubMed id: 16326711

Differential Recognition of the Type I and II H Antigen Acceptors by the Human ABO(H) Blood Group A and B Glycosyltransferases.

J.A.Letts, N.L.Rose, Y.R.Fang, C.H.Barry, S.N.Borisova, N.O.Seto, M.M.Palcic, S.V.Evans.

ABSTRACT

The human ABO(H) blood group A and B antigens are generated by the homologous glycosyltransferases A (GTA) and B (GTB), which add the monosaccharides GalNAc and Gal, respectively, to the cell-surface H antigens. In the first comprehensive structural study of the recognition by a glycosyltransferase of a panel of substrates corresponding to acceptor fragments, 14 high resolution crystal structures of GTA and GTB have been determined in the presence of oligosaccharides corresponding to different segments of the type I (alpha-l-Fucp-(1-->2)-beta-d-Galp-(1-->3)-beta-d-GlcNAcp-OR, where R is a glycoprotein or glycolipid in natural acceptors) and type II (alpha-l-Fucp-(1-->2)-beta-d-Galp-(1-->4)-beta-d-GlcNAcp-OR) H antigen trisaccharides. GTA and GTB differ in only four "critical" amino acid residues (Arg/Gly-176, Gly/Ser-235, Leu/Met-266, and Gly/Ala-268). As these enzymes both utilize the H antigen acceptors, the four critical residues had been thought to be involved strictly in donor recognition; however, we now report that acceptor binding and subsequent transfer are significantly influenced by two of these residues: Gly/Ser-235 and Leu/Met-266. Furthermore, these structures show that acceptor recognition is dominated by the central Gal residue despite the fact that the l-Fuc residue is required for efficient catalysis and give direct insight into the design of model inhibitors for GTA and GTB.

Selected figure(s)

Figure 3.
Environment surrounding the Gal monosaccharide in GTA (left) and GTB (right) showing how the critical residues affect acceptor recognition. Atoms in the protein are colored red for oxygen, white for carbon, and blue for nitrogen. Water molecules are shown as cyan spheres. Hydrogen bonds are shown by green dotted lines. Acceptor fragments are shown in yellow.

Figure 4.
Environment surrounding the disaccharide acceptor fragment analogs Lac, βMeLac, and LacNAc (a, b, and d) in GTB and LacNAc in GTA (c) showing how the critical residues affect acceptor recognition. Atoms in the protein are colored red for oxygen, white for carbon, and blue for nitrogen. Water molecules are shown as cyan spheres. Hydrogen bonds are shown by green dotted lines. Acceptor fragments are shown in yellow.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 3625-3632) copyright 2006.

Figures were selected by the author.